Process for preparing MeO-Peg-protected dihydroquinine or dihydroquinidine derivatives, new dihydroquinine or dihydroquinidine derivatives and their use

ABSTRACT

Process for the formation of MeO-Peg-protected dihydroquinine or dihydro quinindine derivatives, new dihydroquinine-or dihyroquinidine derivatives as well as the use thereof. It is known that dihydroquinine or dihydroquinidine derivatives can be successfully used as ligands in the enantioselective dihydroxylation. The new disclosed ligand systems based on dihydroquinine/quinidine, unlike the prior art ligands, can be recycled after enantioselective dihydroxylation by precipitating and filtering the reaction medium, and be reused in the reaction medium. Also disclosed are the ligand systems (I) and (IV), process for preparing the same and their use in the enantioselective dihydroxiation of double bonds.

RELATED APPLICATIONS

This application is a continuation in part of U.S. Ser. No. 09/308,210filed Jun. 25, 1999 as a 371 of PCT/EP97/06396 filed Nov. 17, 1997claiming priority of German Application SN 196 47 889.5 filed Nov. 20,1996.

FIELD OF THE INVENTION

Process for preparing meo-peg-protected dihydroquinine ordihydroquinidine derivatives

DISCUSSION OF RELATED ART

In Chem. Rev. 1994, 94, 2483 (Sharpless, et al), there are describedmonomeric catalyst systems for enantioselective dihydroxylation based ondihydroquinine and dihydroquinidine derivatives. Although theinantio-selectivity of the charged catalysts is very high, the chargedligands are disadvantageous in the respect that it is difficult or notpossible to recycle them and where this is possible, only with pooryield (liquid-liquid extraction yield clearly under 80%).

In J. Am. Chem. Soc. 1996, 118, 7632-3 (Janda, et al), there ismentioned the formation of MeO-Peg-protected dihydroquinine, as well asits application in the enantioselective dihydroxylation of double bondcontaining compounds. The catalyst system mentioned therein achieves theenantioselective dihydroxylation of standard compounds at a level up to30% worse ee levels as the original system found in Sharpless, et al.

TABLE 1 ee-Value ee-Value Nr. Olefin Charged Janda et al. Sharpless etal. 1

88% 99% 2

60% 99% 3

85% 98% 4

43% 98%

In Table 1 there are set forth the best enantioselectivities achieved byJanda, et al and Sharpless, et al, in the dihydroxylation of standardcompounds with their catalyst or ligand systems. Clearly, the polymerbinding of the ligand system under the reaction conditions optimized fora single system, leads to drastically worse ee values.

SUMMARY OF THE INVENTION

The invention refers to new dihydroquinine or dihydroquinidinederivatives of Formulas (I) and (IV), obtainable by the procedures ofthe present invention, as well as their use for the enantioselectivedihydroxylation of double bonds.

The task of the invention was therefore to develop a procedure for theformation of a catalyst system, which gives rise to good ee values suchas in the original Sharpless procedure during dihydroxylation and whichcan be readily separated from the reaction mixture and so becomesavailable for a new reaction cycle. The task of the invention wasfurther the provision of new catalyst systems that can serve for theasymmetric dihydroxylation of double bonds, as well as the manner anduse of their application.

The invention involves a procedure for the manufacture of dihydroquininederivatives of Formula (I)

wherein m is a whole number in the range of 50 to 150, n is a wholenumber in the range of 1 to 5 and z is a whole number in the range of 0to 4,

R₁, R₂, and R₃ independently of each other are the same or different, R₂and R₃ depend upon a variable n, and these have value H, (C₁-C₅)-alkyl,being linear or branched, (C₃-C₈)-cycloalkyl, aryl, aralkyl, alkylarylor (C₁-C₈)-alkylalkoxy (sic) which may be linear or branched, and

R is a residue of Formula (II) or (III)

wherein R′ is hydrogen, (C₁-C₅) alkyl being linear or branched, (C₃-C₈)cycloalkyl, aryl, aralkyl or alkylaryl,

as well as for the formation of dihydroquinidine derivatives of Formula(IV)

wherein m and p independently of each other are the same or differentwhole numbers in the range of 50-150, n and o independently of eachother are whole numbers in the range of 1-5 and z and y independently ofeach other are the same or different whole numbers in the range of 0through 4, and R, R₁, R₂, and R₃ have the same meaning as in Formula (I)wherein R₂ and R₃ are thereby additionally dependent upon variable o.

When one esterifies compounds of Formula (I) or (VI) with compounds ofgeneral Formula (VIII) (see scheme 1), one can obtain compounds ofFormulas (II) and (IV) respectively with considerable advantage whichcan be employed in the enantioselective dihydroxylation with unforeseensuccess.

The compounds of Formula (V) and (VI) can furthermore be obtained whenone reacts compounds of Formulas (VIII) and (IX) with the aromaticcompound (X) in the presence of catalytic amounts of a palladium ^(±0)compound (see scheme 2) and subsequently removes the silyl protectinggroup with a fluoride containing agent. It is particularly preferredherein to charge tetrabutyl ammonium fluoride.

The charged palladium compound comprises advantageously of the elementalmetal and a complexing ligand from the series of triphenylphosphine ortriphenylphosphite. Particularly preferred is the compound [Pd(PPh₃)₄].

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The compounds of Formulas (VIII) and (IX) can be obtained in differentways.

In a first preferred embodiment, the procedure is characterized therebythat the compound of Formula (VIII)

is obtained by reaction of a substance of Formula (XII)

with DHQ (II) or DHQD (III).

In a second preferred embodiment, the process of the present inventionis characterized thereby that a compound of Formula (IX)

is obtained by reaction of a substance of Formula (XIII)

with a DHQ (II) or DHQD (III).

The substances of Formulas (XIII) and (XII) can be prepared in a manneranalogous to the procedures known in the literature (J. Org. Chem. 1993,58, 3785), starting from 4-bromo benzonitrile orpyrazine-2,3-dicarboxylic acid in accordance with, for example, J. Org.Chem. 1995, 60, 3940.

The new ligand systems of Formulas (I) and (V) are furthermore thesubject of the present invention.

The object of the present invention is also the use of the new ligandsystems (I) and (IV) which advantageously permit, in the presence ofoxidizing agents such as N-methylmorpholine-N-oxide, potassiumhexacyanoferrate and/or potassium osmate in a solvent mixture to thedihydroxylation of a double bond in very high enantiomeric excess. Apreferred use in accordance with this invention provides that thedihydroxylation is carried out in a solvent mixture containing one ormore of the solvents of the group: water, alcohols such as methanol,ethanol, isopropanol, N-propanol, N-butanol, secondary butanol,tert.-butanol, isobutanol, N-pentanol; ethers such as diethylether,tetrahydrofuran, dimethoxy ethane, dioxane; ketones such as acetone,methyl isobutyl ketone, ethyl ketone (sic), diisopropyl ketone; oresters such as acetyl acetic esters or acetic esters, as well ashalogenated alkanes such as methylene chloride, chloroform, andtrichlorethylene. Preferred solvent mixtures are among others, watertert.butanol, or water acetone. It is particularly advantageous toprovide the solvent mixture from at least two of the above-namedsolvents. Furthermore, the catalysts (I) and (IV) can be readilyprecipitated after the dihydroxylation by the addition of non-polarorganic solvents to the reaction mixture. To the hereto preferredaddable solvent materials, there may be counted for example, alkane,such as hexane, cyclohexane, methylcyclohexane; petroleum ethers orether (sic). Preferred are MTBE, tetrahydrofuran or diethylether as wellas DME; ketone, such as acetone, MIBK or ethylmethyl ketone, as well asdiisopropyl ketone; esters such as acetic ester or acetyl acetic ester.The temperature of the dihydroxylation lies between −20° C. to +20° C.,preferred at temperatures between −10° to +10° C., particularlypreferred are temperatures from +2° to −2° C. The recycling occurs asshown in Scheme (III).

TABLE 2 R,R′,R″ Cat. % ee* % ee⁺ Ph,H,Ph (IV) 99% 99% Ph,H,H (IV) 98%99% Ph,Me,H (IV) 95% 96% C₈H₁₇,H,H (I) 87% 89% Me₃C,H,H (I) 90% 92%*Present Invention ⁺Sharpless

Table 2 shows the enantioselectivity obtained in the dihydroxylation ofstandard compounds in accordance with Example 1 in comparison to thoseobtainable in the catalyst system of Sharpless, et al. The ee values inaccordance with the present invention lie minimally lower. After removalof the ligands from the reaction mixture by precipitation with non-polarsolvents in over 80% yield, these can be introduced into a newdihydroxylation which is particularly advantageous and quite unexpected.

Table 3 shows the results obtained in a dihydroxylation of styrene, in amanner analogous to Example I in a 6 times sequential introduction ofthe ligand (IV). The very mild reduction of the ee values is due to lossof alkaloid through minimal ester hydrolysis under the basic conditionsof the reaction.

TABLE 3 Charged Ligand (IV) Run Charged Olefin ee-Value 1

98% 2 ″ 98% 3 ″ 98% 4 ″ 98% 5 ″ 97% 6 ″ 96%

The reaction may optionally be carried out continuously in suitableinstallation in that one operates with polymer ligands of Formulas (I)of (IV) in a loop reactor and contacts the solution with the compound tobe hydroxylated before the dihydroxylation and, after the end of thereaction, separates them by suitable appliances with or withoutprecipitation of the ligands, but with retention of same in the loopreactor.

It is therefore possible to charge the expensive new ligand systems (I)and (IV) for the highly enantioselective dihydroxylation andsubsequently to recycle them in a simple manner most advantageously andin very good yields, which contributes to the economically desirableproduction of enantioselectively enriched 1,2-diols.

The following examples serve to illustrate the invention:

A: Reaction Example EXAMPLE 1

Dihydroxylation of Styrene

A mixture of 167 mg (15 μmol) (MeOPEG)₂DPP(DHQD)₂, 0.99 g (3 mmol)potassium hexacyanoferrate (III), 0.41 g (3 mmol) potassium carbonateand 3.7 mg (10 μmol) potassium osmate in 10 ml t-butanol/water 1:1 werecooled to 0° C. in an ice bath. To this reaction solution, 104 mg (1mmol) styrene was dripped in under vigorous stirring. After 4 hours, thereaction mixture is treated with 1 g sodium disulfide at 0° C. withcare, and allowed to warm to room temperature. The mixture is dilutedwith 10 ml methylene chloride and separated from the aqueous phase. Theligand is precipitated from the aqueous phase by the slow dripping in ofMTBE with vigorous stirring and recovered in good yield (164 mg, 98%).The dihydroxylated styrene remains in the organic solution and can beisolated by concentration and chromatography on silica gel with MTBE inyields of up to 127 mg (92% of theory) and 98% ee.

B: Preparation of the Ligand EXAMPLE 2

Synthesis from 4-Bromobenzamidene Hydrochloride

To a solution of 0.35 g (15 mmol) of sodium in 150 ml of methanol, therewere added 27.30 g (150 mmol) of 4-bromobenzonitrile. Under stirring 48hours at room temperature 8.0 g (150 mmol) of ammonium chloride wereadded and stirred for a further 24 hours. The surplus ammonium chloridewas filtered off and washed with methanol and methylene chloride (100 mlin each case). After removal of the solvents, there is provided acolorless solid which were subsequently washed with 150 ml diethylether. The yield was 11.76 g (50 mmol), 33% theory.

The ether wash solution can be concentrated to yield 16.57 g (91 mmol)of recovered 4-bromobenzonitrile.

¹H-NMR (300 MGz, DMSO-d₆):□3.17 (s, 4H; NH), 7.80-7.92 (m, 4H; Ar-H).

Synthesis of 2-(4-bromophenyl)-5-phenyl-4,6-dihydroxypyrimidine

Into a solution of 3.45 g (150 mmol) of sodium in 100 ml methanol, therewere sequentially added 10.98 g (47 mmol) 4-Bromobenzamidenehydrochloride and 11.15 g (47 mmol) of phenyl malonic acid ethyl ester.The mixture was heated for 12 hours at 80° C. The deep yellow reactionsolution was filtered to remove the precipitated sodium chloride andthereafter the pyrimidine was precipitated with 10 ml of 2 molarhydrochloric acid as an intensive yellow solid. The solid wassequentially washed with water, ethanol and diethyl ether. Yield: 12.70g (37 mmol, 79% theory) of yellow solid. The pyrimidine is insoluble inall tested organic solvents as well as in water.

m.p. greater >230° C.; High Resolution Mass Spectroscopy (FD):calculated for C₁₆H₁₁BrN₂O₂ (M⁺), 342.0009; Found: 342.0009.

Synthesis of 2-(4-bromophenyl)-5-Phenyl-4,6-dichloropyrimidine

A mixture of 11 g (32 mmol)2-(4-bromophenyl)-5-phenyl-4,6-dihydroxypyrimidine, 120.6 g (0.79 mmol)phosphoryl chloride and 10.26 g (69 mmol) N,N-diethylaniline was heatedfor 48 hours at 130° C. The surplus phosphoryl chloride was distilledoff and the hot residue freely poured onto a mixture of sodium hydroxideand ice (27 g/270 g) under stirring. Thereafter, extraction was carriedout three times with 60 ml diethylether each time. Combined organicphases were sequentially treated with hydrochloric acid, washed neutralwith water, dried over magnesium sulfate, filtered and concentratedunder reduced pressure. Recrystallization of the residue from aceticester hexane yields 9.12 g (25 mmol, 75% theory of colorless needless.

m.p.: 133° C. Elemental analysis: C₁₆H₉Cl₂BrN₂ (380.07 g/mol); Calc. C50.56, H 2.39, N 7.37; Found: C 50.54, H. 2.47, N 7.38.

Synthesis of2-(4-bromophenyl)-4-phenyl-4,6-bis-(dihydroquinidine)-pyrimidine

To 1.62 g (4.26 mmol) 2-(4-bromophenyl)-5-phenyl-4,6-dichloro-pyrimidineand 2.78 g (8.53 mmol) dihydroquinidine in 25 ml toluene, there is added1.8 g (13 mmol) potassium carbonate and the mixture heated for 2 hoursat 130° C. Subsequently, 0.73 g (13 mmol) potassium hydroxide were addedand the mixture boiled under a water separator. The toluene is distilledoff and the residue taken up in 15 ml of methylene chloride and shakenthree times with 10 ml of water each time. The combined organic phaseswere dried over magnesium sulfate, filtered and concentrated undervacuum. Purification by column chromatography (silica gel, eluentchloroform/ethanol 9:1) yielded 3.06 g (3.2 mmol, 75% theory) of aweakly yellow solid.

m.p. 125-128° C.

Synthesis of2-(4-Hydroxybiphenyl)-5-phenyl-4,6-bis(dihydroquinidine)-pyrimidine

To a solution of 1.44 g (1.5 mmol)2-(4-bromophenyl)-5-phenyl-4,6,-dichloropyrimidine and 0.132 g (0.11mmol) of tetrakis(triphenyl-phos-uine) palladium in 15 ml of 2 molarsodium carbonate solution and 45 ml of toluene, there were slowly added0.75 g (1.88 mmol) of 4-(tert. butyidimethylsilyloxy)-phenyl boric acidin 21 ml of methanol. Subsequently, the mixture was heated under refluxfor 24 hours. After cooling, the mixture was diluted with methylenechloride and water with, in each case, 50 mls. The aqueous phase wasseparated and extracted three times with 10 ml of dichloromethane. Theorganic phases were combined and dried over magnesium sulfate andconcentrated in vacuum. After chromatography on silica gel with MTBE (toremove the surplus boric acid), there was yielded a weakly yellow solid.This was dissolved 35 ml of THF, cooled to 0° C. and slowly treated with3 ml (3 mmol) of tetrabutyl ammonium fluoride (1 molar in THF). Themixture was then stirred for 15 minutes at 0° C. and for 45 minutes atroom temperature. After quenching with 30 ml of water, the THF wasremoved under vacuum and the residue extracted three times with 10 mlmethylene chloride. The combined organic phases were washed with 30 mlof water, dried over magnesium sulfate, filtered and concentrated invacuo. Cleaning with column chromatography (silica gel; eluent:chloroform/ethanol 9:1) yielded 1.0 g (1.13 mol, 75% of theory) of aweakly yellow solid.

m.p. 178° C.

Synthesis of[2-(4-hydroxybyphenyl)-5-phenyl-4,6-bis(dihydroquinidine)-pyrimidinyl-polyethyleneglycol succinate

To a mixture of 1.95 g (2 mmol)2-(hydroxybiphenyl)-5-phenyl-4,6-bis(dihydroquinidine)pyrimidine, 5.10 g(mmol) succinic acid polyethylene glycol ester (mono ester) and 0.024 g(0.2 mmol) 4-dimethylaminopyridine (DMAP), 0.454 g (2.8 mmol)dicyclohexylcarbodiimide (DCC) were added. The mixture was stirred for12 hours at room temperature. The precipitated dicyclohexyl urea wasfiltered off. Subsequently, tert butyl methyl ether (MTBE) was addedslowly under vigorous stirring and the precipitate was filtered off. Theweakly yellow solid was taken up twice in a small amount of methylenechloride and again precipitated with MTBE. The yield is 5.63 g (0.93mmol), 93% of theory) of a light yellow solid.

m.p.: 56-59° C.

¹H-NMR (300 MHz, CDCl₃)□=0.66 (t, J=7.2 Hz; 6 H), 0.92 (m, 4H),1.19-1.83 (m, 10H), 1.95 (m, 2H), 2.48-3.01 (m, 12H), 3.2-2.9(Polyethylene glycol peaks), 6.9-7.75 (m, 21H) 8.05 (d, J=9.04 Hz; 2H),8.79 (m, 2H).

EXAMPLE 3

Synthesis of23-bis(4-bromophenyl-5,8-dihydroxypyrazino-[2,3-d]-pyridazine

A solution of 7.11 g (50 mmol) 4,5-diamino-3,6-dihydroxy pyridazine and20 g (54 mmol) 4,4′-dibromobenzyl (sic) (dibromobenzene) in 400 ml ofglacial acetic acid were heated for 5 hours at 110° C. (after 10 minutesa yellow precipitate is formed). It was gradually cooled down to roomtemperature, the precipitate filtered off, and washed twice with 50 mlglacial acetic acid and twice with N-hexane. The yield is 19.03 g (40mmol, 80% of theory) of a yellow solid.

m.p.:>240° C. Elemental analysis: C₁₈H₁₀Br₂N₄O₂ (474.11 g/mol); Calc. C45.60, H 2.13, N 11.82; Found: C 45.81, H 2.29, N 11.85.

Synthesis of2,3-bis(4-bromphenyl)-5,8-dichlorotriazine-[2,3-d]-pyridazinyl

A mixture of 180 g (38 mmol)2,3-bis(4-bromophenyl)-5,8-di-ydroxypyrazino-[2,3-d]-pyridazinyl and15.81 g (756 mmol) phosphorus pentachloride in 200 ml phosphorylchloride was heated for 90 minutes at 120° C. Subsequently, thephosphoryl chloride was removed in vacuum and the residue taken up in 50ml ethylene chloride. 6 g of basic aluminum oxide were added and afterfiltration over silica gel, there is yielded 17.67 g (34 mmol), 91% oftheory) of a yellow solid.

m.p. 214-218° C.

Synthesis of2,3-bis(4-bromophenyl)-5,8-bis-(dihydroquinidine)-pyrazino-[2,3-d]-pyridazinyl

To a solution of 0.734 g (2.25 mmol) dihydroquinidine and 0.581 g (5mmol) N,N,N′,N′-tetramethyl ethylene diamine in 16 ml dimethoxy ethanewere cooled to −50° C. and slowly reacted with 1.4 mol (2.25 mmol)N-butyl lithium (15% solution in hexane). The red solution was stirredfor 15 minutes, permitted to warm to room temperature and treated with0.511 g (1 mmol) 2,3-Bis(4-bromophenyl)-5,8-dichlorotriazine-[2,3-d]-pyridazinyl solution. Subsequently, itwas heated under reflux for 4 hours and diluted with 5 ml water and 25ml methylene chloride. The mixtures were washed with 20 ml of saturatedsodium hydrogen carbonate solution and the aqueous phase extracted threetimes with 20 ml methylene chloride. The combined organic extracts weredried over magnesium sulfate, filtered and concentrated under reducedpressure. Purification through column chromatography (silica gel;eluent; chloroform-ethanol 9:1 yielded 0.796 g (0.73 mmol) 73% theory.

m.p. 176-180° C.

Synthesis of 5,8-Bis-(Dihydroquinindinyl)2-3,bis-(4-hydroxybiphenyl)-pyrazino-[2,3-d]-pyridazine

To a solution of 19.56 g (18 mmol)2,3-Bis(4-bromiphenyl)-5,8-bis-(dihydroquinindinyl)-pyrazino[2,3-d]-pyridazineand 0.5 g (0.433 mmol) tetrakis-triphenylphosphine)-palladium in 500 mltoluene and 200 ml 2 molar sodium carbonate solution, there was slowlyadded 13.56 g (54 mmol) of 4-(tert butyl dimethyl silyloxy)-phenyl boricacid in 800 ml methanol. Subsequently, the mixture was heated underreflux for 24 hours. After cooling, a separated aqueous phase wasextracted three times with 100 ml methylene chloride and, the combinedorganic phases dried over magnesium sulfate, filtered and concentratedin vacuum. After column chromatography on silica gel with MTBE (forremoval of excess boric acid), there is obtained a yellow solid. Thiswas dissolved in 200 ml THF and slowly treated at 0° C. at 72 ml (72mmol) with tetrabutyl ammonium fluoride (1 molar in THF). Subsequentlythe mixture was stirred for 15 minutes at 0° C. and 45 minutes at roomtemperature. After quenching with 350 ml of water, the THF was removedunder vacuum and the residue extracted with 300 ml ethanol/methylenechloride 1:1. The organic phase was washed three times with 100 ml ofwater, dried over magnesium sulfate, filtered and concentrated invacuum. Purification through column chromatography (silica gel; eluent,chloroform-ethanol 8:2) yielded 13.68 g (12.2 mmol), 68% of theory)yellow solid.

m.p.: 204-209° C.

Synthesis of[5,8-Bis(dihydroquinindinyl)-2,3-bis-(4-hydroxybiphenyl)-pyrazino-[2,3-d]-pyridazinyl-polyethyleneglycol-succinate

To a mixture of 1.34 g (1.2 mmol)5,8-Bis-(dihydroquinindinyl)-2,3-bis(4-hydroxybiphenyl)-pyrazino-[2,3-d}-pyridazine,13.26 g (2.6 mmol) polyethylene glycol succinate (monoester) and 32 mg(0.26 mmol) DMAP, there was added 2.7 g (13 mmol) of DCC. The mixturewas stirred for 48 hours at room temperature and the precipitateddicyclourea was filtered off. MTBE was dripped slowly into the stronglystirred filtrate and thus produced precipitate filtered off. The yellowsolid was twice taken up in a small amount of methylene chloride andagain precipitated with MTBE. The yield was 12.24 g (1.10 mmol, 92% oftheory) of yellow solid. m.p.: 55-58° C.

Synthesis of 4-Bromophenyl-tert.butyldimethylsilyl ether

To a solution of 31.13 g (180 mmol) 4-bromophenol and 32.55 g (216 mmol)tert.butyldimethyl silyl chloride in 600 ml methylene chloride there wasadded 29.4 g (432 mmol) imidazole. The mixture was stirred for 12 hoursat room temperature. After quenching with 1000 ml of water, the aqueousphase was separated and extracted with MTBE (200 ml 3 times). Combinedorganic phases were washed with saturated sodium chloride solution,dried over magnesium sulfate, filtered off and concentrated in vacuo.Purification through column chromatography (silica gel; eluate MTBE)yielded 50.15 g (17.4 mmol, 97% of theory) of a clear colorless oil.

Elementary analysis: C₁₂H₁₉BrOSi (287.27 g/mol) Calc.: C 50.17 H 6.67;Found: C 50.24 H 6.70.

Synthesis of 4-(tert.Butyldimethyl silyloxyl)-phenyl boric acid

To a suspension of 0.53 g (22 mmol) of magnesium shavings in 200 ml ofTHF was added 0.5 ml of 5.75 g (20 mmol) (sic) 4-bromophenyl-tert butyldimethyl silyl ether and a drop of 1,2-dibromo methane. The reactionmixture was briefly heated to reflux to commence the reaction.Subsequently, the rest of the aryl bromide was dripped in slowly. Aftercessation of the addition, reflux was continued for a further hour. Thecopper colored solution was cooled to room temperature and addeddropwise to a solution of 10.39 g (0.1 mmol) trimethyl borate in 50 mlTHF previously cooled to −78° C. The mixture was permitted to rise toroom temperature overnight. The mixture was quenched with 30 ml of waterand the THF removed under vacuum. The residue was extracted three timeswith MTBE, the combined organic phases dried over magnesium sulfate,filtered and concentrated in vacuo. Purification by columnchromatography (silica gel; eluent MTBE) yielded 4.09 g (16.2 mmol, 81%of theory) of a colorless solid.

¹H-NMR (300 MHz, Acetone-d₆):□=0.22 (s, 6H; CH₃) 0.99 (s, 9H; tBu), 6.86(m, 2H; Ar-H), 7.79 (s, 2H; Ar-H). Elementary analysis: C₁₂H₂₁BO₃Si(252.19); Calc.: C_(57.15) H 8.39; Found: C 60.16 H 8.44.

What is claimed is:
 1. A ligand of Formula (IV)

wherein m and p independently of each other may be equal or differentintegers in the range of 50 to 150, n and o independently of each otherare the same or different integers in the range of 1 to 5 and z and yindependent of each other are the same or different integers in therange of 0 to 4, and R₁, R₂ and R₃ independently of each other are equalor different, and R₂ and R₃ depend from n variable, H, (C₁-C₅)-alkyl,linear or branched, (C₃-C₈)-cycloalkyl, aryl, aralkyl, alklaryl or(C₁-C₈)-alkylalkoxy, linear or branched, and wherein R₂ and R₃additionally depend from the variable o and R is a residue selected fromthe group consisting of Formula (II) and (III)


2. A process for the preparation of a ligand of Formula (IV)

wherein m and p independently of each other may be equal or differentintegers in the range of 50 to 150, n and o independently of each otherare the same or different integers in the range of 1 to 5 and z and yindependent of each other are the same or different integers in therange of 0 to 4, and R₁, R₂ and R₃ independently of each other are equalor different, and R₂ and R₃ depend from n variable, H, (C₁-C₅)-alkyl,linear or branched, (C₃-C₈)-cycloalkyl, aryl, aralkyl, alklaryl or(C₁-C₈)-alkylalkoxy, linear or branched, and wherein R₂ and R₃additionally depend from the variable o, which comprises esterifyingintermediate products of Formula (VI),

and R is a residue selected from the group consisting of Formula (II)and (III)

wherein R′ stands for H, (C₁-C₅)-alkyl, linear or branched chain,(C₃-C₈)-cycloalkyl, aryl, aralkyl or alkylaryl with a compound ofFormula (VII),

wherein m, n and z as well as R₁, R₂ and R₃ have the meanings given for(IV).
 3. The process in accordance to claim 2 which comprises producingthe intermediate products of Formula (VI) by the reaction of compoundsof Formula (IX)

wherein R is a residue of Formula (II) or (III) with a compound ofFormula (X)

in the presence of catalytic amounts of palladium and subsequentlysplitting the silyl group by reaction with a fluoride containingreagent.
 4. The process according to claim 2 wherein the catalyticallyactive palladium has the oxidation level ±0 and is complexed with atriphenyl phosphine or triphenyl phosphite ligand.
 5. The processaccording to claim 3, wherein the catalytically active palladium is acompound of Formula (XI) [Pd(PPH₃)₄]  (XI).
 6. The process in accordancewith claim 2 wherein the silyl group splitting reagent is a tetraalkylammonium fluoride.
 7. A process for the catalytic enantioselectivedihydroxylation of double bonds in a solvent in the presence of anoxidizing agent wherein the ligands are selected from the groupconsisting of compounds of Formula (IV)

wherein m and p independently of each other may be equal or differentintegers in the range of 50 to 150, n and o independently of each otherare the same or different integers in the range of 1 to 5 and z and yindependent of each other are the same or different integers in therange of 0 to 4, and R₁, R₂ and R₃ independently of each other are equalor different, and R₂ and R₃ depend from n variable, H, (C₁-C₅)-alkyl,linear or branched, (C₃-C₈)-cycloalkyl, aryl, aralkyl, alklaryl or(C₁-C₈)-alkylalkoxy, linear or branched, and wherein R₂ and R₃additionally depend from the variable o and R is a residue selected fromthe group consisting of Formula (II) and (III)


8. The process of claim 7 which comprises precipitating the compound ofFormula (IV) after the dihydroxylation, and separating them byfiltration from the reaction mixture whereby they can again beintroduced into the reaction.
 9. The process of claim 7 which comprisescarrying out the dihydroxylation at a temperature of between −20 and+20° C.
 10. The process of claim 7 wherein the solvent is a solventmixture containing one or more solvents of the group: water, alcohols,ethers, ketones esters and halogenated alkanes.
 11. The process of claim7 wherein the alcohol is methanol, ethanol, isopropanol, n-propanol,n-butanol, secondary butanol, tert. butanol, isobutanol or n-pentanol,the ether is diethyl ether, tetrahydrofuran, dimethoxy ethane or dioxan,the ketone is acetone, methyl isobutyl ketone, ethyl ketone ordiisopropyl ketone, the ester is acetyl acetic ester or acetic ester,and the halogenated alkane is methylene chloride, chloroform ortrichloroethylene.
 12. The process in accordance with claim 7 whereinthe oxidizing agent is of potassium hexacyanoferrate or methylmorpholine oxide alone or in the presence of potassium osmate.
 13. Theprocess in accordance with claim 12 wherein the oxidizing agent ispotassium hexacyanoferrate and potassiium osmate.
 14. The process in accordance with claim 12 wherein the oxidizing agent is N-methylmorpolineoxide and potassium osmate.